Degenerative joint disease, particularly knee osteoarthritis (OA), is one of the most prevalent and disabling chronic pain conditions and is projected to increase sharply as the U.S. population ages. Projections also indicate that the annual number of total knee replacements, the treatment of choice for end-stage knee OA, will increase five- to ten-fold in the U.S. over the next several decades. While the outcomes following total knee arthroplasty are generally good, a substantial minority of patients continue to experience significant long-term pain and disability after surgery. These individual differences in the trajectory of pain and function after knee replacement are minimally related to findings from physical examination and imaging procedures. Our group has identified several potentially important variables that are likely to play a role in shaping long-term pain outcomes, though there are few published studies in patients with knee OA. The proposed 2-site prospective cohort project will carefully evaluate and follow a sample of patients undergoing total knee replacement. Knee OA patients will be assessed pre-surgically with a battery of psychophysical pain testing procedures, multimodal evaluation of sleep quality, continuity, and architecture, questionnaires regarding psychological function, and physiological sampling (e.g., blood and saliva samples). Outcomes such as pain, functioning, and analgesic usage will be evaluated through 12-month follow-up. These data will allow us to model the unique and combined impact of these classes of "risk factor" variables. Collectively, the identification of factors associated with the development and maintenance of persistent pain and pain-related disability following joint replacement has important practical implications for selection of surgical patients and for management of post-operative pain, as well as theoretical importance in understanding the sources of individual differences in pain-related outcomes. PUBLIC HEALTH RELEVANCE: Chronic pain is a critical national and international health problem, making the identification of groups at high risk for the development or persistence of chronic pain an increasingly important area of investigation. This project seeks to identify risk factors for persistent pain and physical disability following total knee replacement, a surgical procedure projected to increase five- to ten-fold in the U.S. over the next several decades. Collectively, the identification of factors associated with the development and maintenance of persistent pain and pain-related disability following joint replacement has important practical implications for the selection of surgical patients, for the management of post-operative pain, and for understanding the sources of individual differences in pain-related outcomes.